The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.

ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

UPJE: Most pharmacy law educators have heard of it, but support remains divided.

Background: Most states require pharmacists to successfully pass the Multistate Pharmacy Jurisprudence Examination (MPJE) required by the National Association of Boards of Pharmacy (NABP) to obtain licensure as a pharmacist, though pass rates for the MPJE have declined in recent years. Meanwhile, NABP is pursing efforts to standardize the exam with the emergent Uniform Pharmacy Jurisprudence Examination (UPJE).

Objective: This study aimed to describe the current thinking of pharmacy law educators across the US on the UPJE.

Assessing the benefit-risk profile of newer glucose-lowering drugs: A systematic review and network meta-analysis of randomized outcome trials.

Aim: To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i).

Materials And Methods: A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.

Relationship Between 1,5 Anhydroglucitol, Glycemia, and Breastfeeding During Pregnancy and Postpartum: A Pilot Study.

Background: Assessments for hyperglycemia are vital to pregnancy and postpartum (PP) care, but gold-standard oral glucose tolerance tests (OGTTs) are burdensome. We examined changes in 1,5 anhydroglucitol (1,5AG) levels during gestation and PP and assessed for associations with other measures of glycemia.

Study Design: Pregnant participants (n = 50) in the Study of Pregnancy Regulation of Insulin and Glucose cohort underwent OGTTs at a mean of 13 weeks ([visit 1 (V1)] and 26 weeks [visit 2 (V2)] of gestation and PP.